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An On-Demand Drug Delivery System for Control of Epileptiform Seizures
https://oist.repo.nii.ac.jp/records/2710
https://oist.repo.nii.ac.jp/records/2710f8191458-f55d-4938-8051-3a50523e4d65
名前 / ファイル | ライセンス | アクション |
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pharmaceutics-14-00468-v2 (15.3 MB)
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Creative Commons Attribution 4.0 International(https://creativecommons.org/licenses/by/4.0/)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2022-07-13 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | An On-Demand Drug Delivery System for Control of Epileptiform Seizures | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | liposome | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | nanoparticle | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | seizure | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | laser | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | ultrasound | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者(英) |
Nakano, Takashi
× Nakano, Takashi× Rizwan, Shakila B.× Myint, David M. A.× Gray, Jason× Mackay, Sean M.× Harris, Paul× Perk, Christopher G.× Hyland, Brian I.× Empson, Ruth× Tan, Eng Wui× Dani, Keshav M.× Reynolds, John NJ× Wickens, Jeffery R. |
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書誌情報 |
en : Pharmaceutics 巻 14, 号 2, p. 468, 発行日 2022-02-21 |
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抄録 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Drug delivery systems have the potential to deliver high concentrations of drug to target areas on demand, while elsewhere and at other times encapsulating the drug, to limit unwanted actions. Here we show proof of concept in vivo and ex vivo tests of a novel drug delivery system based on hollow-gold nanoparticles tethered to liposomes (HGN-liposomes), which become transiently permeable when activated by optical or acoustic stimulation. We show that laser or ultrasound simulation of HGN-liposomes loaded with the GABAA receptor agonist, muscimol, triggers rapid and repeatable release in a sufficient concentration to inhibit neurons and suppress seizure activity. In particular, laser-stimulated release of muscimol from previously injected HGN-liposomes caused subsecond hyperpolarizations of the membrane potential of hippocampal pyramidal neurons, measured by whole cell intracellular recordings with patch electrodes. In hippocampal slices and hippocampal–entorhinal cortical wedges, seizure activity was immediately suppressed by muscimol release from HGN-liposomes triggered by laser or ultrasound pulses. After intravenous injection of HGN-liposomes in whole anesthetized rats, ultrasound stimulation applied to the brain through the dura attenuated the seizure activity induced by pentylenetetrazol. Ultrasound alone, or HGN-liposomes without ultrasound stimulation, had no effect. Intracerebrally-injected HGN-liposomes containing kainic acid retained their contents for at least one week, without damage to surrounding tissue. Thus, we demonstrate the feasibility of precise temporal control over exposure of neurons to the drug, potentially enabling therapeutic effects without continuous exposure. For future application, studies on the pharmacokinetics, pharmacodynamics, and toxicity of HGN-liposomes and their constituents, together with improved methods of targeting, are needed, to determine the utility and safety of the technology in humans. | |||||
出版者 | ||||||
出版者 | MDPI | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1999-4923 | |||||
PubMed番号 | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | PMID | |||||
関連識別子 | info:pmid/35214199 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | info:doi/10.3390/pharmaceutics14020468 | |||||
権利 | ||||||
権利情報 | © 2022 The Authors. | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://www.mdpi.com/1999-4923/14/2/468 | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 |